生物谷报道：T4病毒的DNA需要在特定“分子马达”（molecular motor）的帮助下才能进入病毒的衣壳。Purdue大学和美国Catholic大学的研究人员最近发现了一种在运转这种发动机中发挥重要作用的酶——ATPase的结构。文章第一作者为Purdue大学科学院Michael Rossmann实验室博士后孙斯阳（Siyang Sun，音译）。详细研究内容刊登于3月22日《Molecular Cell》。
这种发动机在其它病毒中也存在，包括人疱疹病毒。“这是首次对与DNA包装发动有关的ATPase的结构进行测定，”Rossmann教授说，“病毒首先组装蛋白头部的蛋白壳，然后将DNA装入空的衣壳中。这种过程可以比喻为建造房屋，然后添加家具。”
DNA记录了病毒的全部特征，衣壳保护了这种记录，确保病毒能够通过感染宿主不断繁殖。ATPase将ATP降解为ADP时，产生运转包装发动机所需的能量。ATPase特意破坏磷酸盐和ADP之间的化学键。
研究人员通过将运转T4病毒的分子马达所需的ATPase的结构与解旋酶（helicases）的结构进行对比，推测了一种可能的马达工作机制。解旋酶是在基因复制过程中将双链DNA分开为单链的酶。DNA复制过程中，解旋酶选择性结合或脱离DNA，如尺蠖一样沿螺旋移动将双链分为单链。研究人员推测马达利用相似的尺蠖机制将DNA挤入病毒中。
研究人员利用X射线结晶学技术分析了ATPase的结构。疱疹和其他病毒也许含有相似的DNA包裹马达，这项发现为设计干扰这些马达的药物、治疗病毒感染、发展微型“纳米马达”提供了参考。
“现在谈论这些发现的潜在应用价值为时尚早，” Rossmann说，“希腊人发现行星时，他们一定不会想到那些发现导致了几百个世纪后的航天轨道（spacecraft trajectories）设计。”该研究主要受美国国家科学基金会和人类前沿科学计划组织（Human Frontier Science Program）资助。
部分英文原文：
Copyright © 2007 Cell Press. All rights reserved.
Molecular Cell, Vol 25, 943-949, 23 March 2007
The Structure of the ATPase that Powers DNA Packaging into Bacteriophage T4 Procapsids
Siyang Sun,1 Kiran Kondabagil,2 Petra M. Gentz,1,3 Michael G. Rossmann,1, and Venigalla B. Rao2,
1 Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN 47907, USA
2 Department of Biology, The Catholic University of America, 620 Michigan Avenue NE, Washington, DC 20064, USA
Corresponding author
Michael G. Rossmann
mr@purdue.edu
Corresponding author
Venigalla B. Rao
rao@cua.edu
Packaging the viral genome into empty procapsids, an essential event in the life cycle of tailed bacteriophages and some eukaryotic viruses, is a process that shares features with chromosome assembly. Most viral procapsids possess a special vertex containing a dodecameric portal protein that is used for entry and exit of the viral genome. The portal and an ATPase are parts of the genome-packaging machine. The ATPase is required to provide energy for translocation and compaction of the negative charges on the genomic DNA. Here we report the atomic structure of the ATPase component in a phage DNA-packaging machine. The bacteriophage T4 ATPase has the greatest similarity to monomeric helicases, suggesting that the genome is translocated by an inchworm mechanism. The similarity of the packaging machines in the double-stranded DNA (dsDNA) bacteriophage T4 and dsRNA bacteriophage 12 is consistent with the evolution of many virions from a common ancestor.
The T4 DNA-Packaging Machine
(A) A schematic diagram shows the T4 procapsid while being filled with DNA. The portal protein, gp20, forms a dodecameric head-tail connector through which the genome enters the procapsid and exits the mature phage. The stoichiometry of the large terminase gp17 oligomer is suggested to be pentameric or decameric. The amino-terminal domain of gp17 has ATPase activity, whereas the carboxy-terminal domain has nuclease activity. There are probably eight to ten gp16 monomers in the small terminase oligomer. The small terminase functions to enhance the ATPase activity of th
